Transcriptomic identification of genes for obesity and insulin resistance in human adipose tissue in a Mexican American population sample drawn from the Veterans Administration Genetic Epidemiology Study (VAGES)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE64567 | GEO | 2014/12/31
SECONDARY ACCESSION(S): PRJNA271323
REPOSITORIES: GEO
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Project description:Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage (GWL) analysis to localize T2DM susceptibility loci in Mexican Americans.We used the phenotypic and genotypic data from 1,122 Mexican-American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). GWL analysis was performed using the variance components approach. Data from 2 additional Mexican-American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence.After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, p = 2.7 × 10(-6)). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region also in SAFDGS, we found the significant and increased linkage evidence (LOD = 4.3, empirical p = 1.0 × 10(-5), genome-wide p = 1.6 × 10(-3)) for T2DM at the same chromosomal region, when we performed a GWL analysis of the VAGES data combined with the SAFHS and SAFDGS data.Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies involving T2DM-related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes.
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Project description:We describe the epidemiology of coccidioidomycosis among a national cohort of Veterans. Using electronic health record data from adults tested for coccidioidomycosis between 1 January 2013 and 31 December 2022, we analyzed differences in baseline demographics (age, sex, race/ethnicity, birth country, comorbidities, residence, and Charlson Comorbidity Index score) between 4204 coccidioidomycosis-test-positive and 63,322 test-negative Veterans. Log-binomial regression models with adjusted risk ratios (aRRs) were used to evaluate risk factors associated with coccidioidomycosis including dissemination, hospitalization, and mortality. Case counts and incidence rates were highest in select counties in Arizona and California where Coccidioides is endemic. Coccidioidomycosis-positive Veterans were younger, more likely to be male, and Philippine-born. The risk factors most highly associated with being coccidioidomycosis-positive included Native Hawaiian/Pacific Islander (aRR 1.068 [95%CI: 1.039-1.098]), Asian (aRR 1.060 [95%CI: 1.037-1.083]), Black (aRR 1.029 [95%CI: 1.022-1.036]), American Indian/Alaska Native (aRR 1.026 [95%CI: 1.004-1.048]) race, and Hispanic/Latino ethnicity (aRR 1.021 [95%CI: 1.013-1.028]). Black race (aRR: 1.058 [95%CI: 1.037-1.081]) and Hispanic/Latino ethnicity (aRR 1.018 [95%CI: 1.0003-1.036]) were also associated with disseminated coccidioidomycosis, strengthening the evidence for the association of coccidioidomycosis, including severe infections, with specific racial and ethnic groups. There were no statistically significant differences in hospitalization within 45 days of testing or 30-day all-cause mortality. Improving our understanding of coccidioidomycosis risk factors is important for targeted prevention strategies and to reduce delays in diagnosis and ineffective treatment.
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Project description:Cryptic population structure can increase both type I and type II errors. This is particularly problematic in case-control association studies of unrelated individuals. Some researchers believe that these problems are obviated in families. We argue here that this may not be the case, especially if families are drawn from a known admixed population such as Mexican Americans. We use a principal component approach to evaluate and visualize the results of three different approaches to searching for cryptic structure in the 20 multigenerational families of the Genetic Analysis Workshop 18 (GAW18). Approach 1 uses all family members in the sample to identify what might be considered "outlier" kindreds. Because families are likely to differ in size (in the GAW18 families, there is about a 4-fold difference in the number of typed individuals), approach 2 uses a weighting system that equalizes pedigree size. Approach 3 concentrates on the founders and the "marry-ins" because, in principle, the entire pedigree can be reconstructed with knowledge of the sequence of these unrelated individuals and genome-wide association study (GWAS) data on everyone else (to identify the position of recombinations). We demonstrate that these three approaches can yield very different insights about cryptic structure in a sample of families.
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Project description:Clinically meaningful behavior problems are thought to be present beginning in the early toddler years, yet few studies have investigated correlates of behavior problems assessed before age 2 years. The current study investigated the direct and interactive contributions of early infant and caregiver characteristics thought to play an important role in the ontogeny of behavior problems. Specifically, the study examined: (a) the links between infant temperamental reactivity and toddler behavioral symptoms, (b) whether maternal sensitivity moderated associations between temperamental reactivity and behavioral symptoms, (c) whether variability in temperamental reactivity was explained by exposure to maternal stressful life events (SLEs) in utero, and (d) whether child sex moderated these pathways. Data were collected from 322 low-income, Mexican American families. Mother reports of SLEs were obtained between 23 and 40 weeks gestation; temperamental negativity and surgency at 6 weeks and 12 months; and internalizing and externalizing behaviors at 18 months. Maternal sensitivity during structured mother-infant interaction tasks at a 12-month visit was assessed by objective raters. Results indicated that significant paths linked maternal prenatal SLEs with 6-week negativity, 6-week negativity with 12-month negativity, and 12-month negativity with 18-month behavioral symptoms. Sex-specific effects were also observed. Maternal SLEs were directly associated with internalizing behaviors for girls only. Surgency and maternal sensitivity moderated the associations of negativity with subsequent externalizing behaviors for girls only. Results suggest that ecological stressors associated with sociodemographic risk factors such as low-income and ethnic minority status begin to exert cascades of influence on children's developmental outcomes even before birth. (PsycINFO Database Record
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Project description:Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES).Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911-2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/ 90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values.The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans.
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Project description:Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10(-4)) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10(-60)) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10(-9)), BMI (5.4 x 10(-6)), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.
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Project description:Background and purposeWe analyzed differences in 90-day poststroke outcomes between Mexican Americans born in the United States (nonimmigrant) compared with those born outside the United States (immigrant).MethodsWe performed a retrospective analysis of prospective data from the population-based Brain Attack Surveillance in Corpus Christi project. We identified stroke cases from 2008 to 2016 and quantified functional, cognitive, and neurological outcomes. Associations between outcome scores and immigration status were analyzed using weighted linear regression models.ResultsEighty-three Mexican American stroke cases (n=935) were immigrants, and 852 stroke cases were nonimmigrants. Average length of stay in the United States for immigrants was 47 years. Immigrants were older (69 versus 66 years), more likely men (60% versus 49%), had less education on average, and were more likely to have atrial fibrillation compared with nonimmigrants. No differences in other comorbidities existed between groups. After adjustment for confounders, immigrants had better functional outcomes (activities of daily living/instrumental activities of daily living; mean difference, -0.22; P=0.02; 1-4, higher scores worse) and no difference in neurological outcomes (log-National Institutes of Health Stroke Scale; mean difference, -0.15; P=0.15; 0-44, higher scores worse) or cognitive outcomes (3 Mini-Mental State Examination; mean difference, -0.79; P=0.64; 0-100, lower scores worse).ConclusionsLong-term Mexican American immigrants in this community display better stroke functional outcomes than nonimmigrant Mexican Americans and comparable neurological and cognitive outcomes.
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Project description:Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes.We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis.After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 +/- 7% (P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 x 10(-5)). This region on 12p harbors the gene-encoding adiponectin receptor 2 (AdipoR2), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES.Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans.
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Project description:ObjectivesTo create a risk index (Mexican American Dementia Nomogram (MADeN)) that predicts dementia over a 10-year period for Mexican Americans aged 65 and older.DesignRetrospective cohort study with longitudinal analysis.SettingTexas, New Mexico, Colorado, Arizona, and California.ParticipantsHispanic Established Populations for the Epidemiologic Study of the Elderly (H-EPESE) participants (n = 1,739).MeasurementsDementia was defined as a decline of three or more points per year on the Mini-Mental State Examination and inability to perform one or more daily activities. Candidate risk factors included demographic characteristics, measures of social engagement, self-reported health conditions, ability to perform daily activities, and physical activity.ResultsThe MADeN comprised the following risk factors: age, sex, education, not having friends to count on, not attending community events, diabetes mellitus, feeling the blues, pain, impairment in instrumental activities of daily living, and unable to walk a half-mile. The area under the receiver operating characteristic curve was 0.74 (95% confidence interval (CI) = 0.70-0.78) and a score of 16 points or higher had a sensitivity of 0.65 (95% CI = 0.59-0.72) and specificity of 0.70 (95% CI = 0.67-0.73) in predicting dementia.ConclusionThe MADeN was able to predict dementia in a population of older Mexican-American adults with moderate accuracy. It has the potential to identify older Mexican-American adults who may benefit from interventions to reduce dementia risk and to educate this population about risk factors for dementia.
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Project description:BackgroundAs part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006, and passed transmission assessment surveys in 2011-2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk.MethodsELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected in 2010. Risk factors assessed for association with sero-positivity included age, sex, years lived in American Samoa, and occupation. Geographic clustering of serological indicators was investigated to identify spatial dependence and household-level clustering.ResultsOg4C3 antigen of >128 units (positive) were found in 0.75% (95% CI 0.3-1.6%) of participants, and >32 units (equivocal plus positive) in 3.2% (95% CI 0.6-4.7%). Seroprevalence of Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3-10.2%) and 17.9% (95% CI 15.3-20.7%) respectively. Antigen-positive individuals were identified in all ages, and antibody prevalence higher in older ages. Prevalence was higher in males, and inversely associated with years lived in American Samoa. Spatial distribution of individuals varied significantly with positive and equivocal levels of Og4C3 antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32 units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity of households explained 85% and 62% of the spatial variation respectively.ConclusionsHigh-risk populations for LF in American Samoa include adult males and recent migrants. We identified locations and estimated the size of possible residual foci of antigen-positive adults, demonstrating the value of spatial analysis in post-MDA surveillance. Strategies to monitor cluster residents and high-risk groups are needed to reduce resurgence risk. Further research is required to quantify factors contributing to LF transmission at the last stages of elimination to ensure that programme achievements are sustained.
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